ARTICLE IN BRIEF
At the 2013 AAN annual meeting, Tobias Kurth, MD, ScD, and colleagues will present data showing that migraine with aura is one of the strongest relative contributors to increased risk of cardiovascular disease events.
Migraine with aura has been previously linked with increased risk of cardiovascular disease (CVD). But the relative contribution of migraine with aura to future CVD events has remained unclear. Now, a new study led by Tobias Kurth, MD, ScD, who is a director of research at the French National Institute of Health and Medical Research (INSERM) as well as associate epidemiologist at Brigham and Women's Hospital, and colleagues, may shed some light on this question. The complete data from this study will be presented at AAN annual meeting in March.
“We tend to think that major risk factors such as hypertension and smoking play a larger role than migraine with aura in contributing to cardiovascular disease,” Dr. Kurth told Neurology Today in a telephone interview. In our study, “we looked at the absolute contributions to the incident rates of cardiovascular disease, and we found that migraine with aura is actually one of the strongest relative contributors. It came ahead of diabetes, current smoking, obesity, and family history of early heart disease.”
According to these findings, he said, having a history of migraine with aura is not something that we should ignore or take lightly when evaluating vascular risk profiles.
This prospective cohort study looked at nearly 28,000 women, aged 45 or older at inclusion, who were participating in the Women's Health Study and were free of CVD at baseline, and for whom there was self-reported information on migraine and lipid measurements.
“The Women's Health Study enrolled female health professionals across the United States starting in 1993, and the study is still in active follow-up. For this study, we assessed baseline information on migraine and other risk factors, and then followed the women for the development of cardiovascular disease during 15 years of follow-up,” Dr. Kurth told Neurology Today in a telephone interview. Using medical records validation, the researchers confirmed major CVD events (nonfatal myocardial infarction, nonfatal stroke, or CVD death).
At baseline, about 5000 women reported migraine, 40 percent of whom reported migraine with aura. During 15 years of follow-up, about 1000 major CVD events were confirmed (overall incidence rate [IR] 2.4 per 1000 women per year). The highest contributor to CVD risk was having a systolic blood pressure greater than or equal to 180mgHg (adjusted IR=9.8). The second strongest single contributor to major CVD risk was migraine with aura (IR = 7.9), followed by diabetes (IR = 7.1), family history of premature myocardial infarction (IR = 5.4), current smoking (IR = 5.4), and body mass index greater than or equal to 35 kg/m2 (IR = 5.3).
The authors concluded, “While the combination of traditional risk factors (i.e., the Framingham risk score) still shows the strongest contribution to CVD occurrence, migraine with aura is a strong relative contributor to increased risk of CVD events.”
This study was funded with grants from the National Institutes of Health.
Richard Lipton, MD, Edwin S. Lowe professor and vice chair of neurology, and professor of epidemiology and population health at Albert Einstein College of Medicine in NY, said that this report is a “major contribution from a large scale epidemiologic study. A prior report from [the Women's Health Study] showed that migraine with aura was a risk factor for cardiovascular disease in women. The new report adds important information on the relative contribution of migraine with aura compared with other well-known risk factors.”
The major strength here is that they followed almost 30,000 women for more than a decade, Dr. Lipton said, “and they did a bang-up job on measuring the vascular risk factors and outcomes.”
One limitation, he said, was that the question used to determine whether women had migraine with aura was simply: “‘Do you have a warning before you get a headache?’ The problem with that question is that there's a difference between auras and prodromes. Auras are actually focal neurologic symptoms that typically precede headache onset, like a graying out of vision, or seeing zigzag lights, or tingling and numbness, or weakness. Prodromes are changes in mood or behavior — such as a difference in fluid balance, being thirsty, being hungry.”
The distinction between prodrome and aura is not entirely clear from the Women's Health Study, he said. “But if the effect of aura is greater than the effect of prodrome, that would make their findings weaker not stronger. So I don't think it could possibly cause a false positive result,” he added.
This result is surprising because it shows that migraine with aura, from a public health perspective, is a more important risk factor than previously thought, Dr. Lipton said. This level of association would also need to be studied in a group of younger women, since this research only included patients who were 45 years of age or older at initial follow up.
We already know that we can prevent migraine attacks by giving preventative medication, noted Dr. Lipton, but “we don't know if treating migraine reduces risk. However, even not knowing that, this study tells us that if we're going to try and intervene on a risk factor to reduce the risk of CVD, migraine with aura would be the second most important one to intervene on.”
IMPLICATIONS, FUTURE RESEARCH
We can't yet say “that a migraine with aura is the cause of these events because we are still missing the understanding of the biology behind these associations. There are several hypotheses that are plausible, which include impaired endovascular function, shared mechanisms leading to both migraine with aura and cardiovascular disease, genetic factors, inflammatory processes, and others,” said Dr. Kurth
“So, what do these findings mean for the practicing neurologist? It is appropriate to discuss them with female patients, especially those who have migraine with aura, and even more so if they are on estrogen products and/or are current smokers,” Alan M. Rapoport, MD, clinical professor of neurology at the David Geffen School of Medicine at University of California in Los Angeles, and president-elect of the International Headache Society (IHS), told Neurology Today.
The clinical implication at this point may be that the patients with migraine with aura and the physicians treating them should know that these patients could be a higher risk group for cardiovascular disease, and they should focus more on the modifiable risk factors, such as hypertension and smoking, Dr. Kurth noted. “Maybe just having a history of migraine with aura should be a flag” for looking at the other risks more carefully, he said.
“An important next step would be to study whether treating migraine — migraine with aura in particular — could reduce the risk of heart attack, stroke, and other poor vascular outcomes in women who have it. The potential is there, but this study doesn't tell us whether intervention would work and it doesn't tell us what the upper bound would be on the amount of disease in the population we could eliminate,” said Dr. Lipton.
We need to target specific questions and have collaboration between population scientists and clinical scientists in order to brainstorm what we can do to understand the mechanisms behind these findings, “and what can we do to provide patients and physicians an answer to their questions,” Dr. Kurth said. In future studies, it is vital to “further pinpoint exactly who is at risk, to what extent, and what can be done to minimize that risk,” Dr. Rapoport agreed.
We don't want these results to scare migraineurs who are already suffering a lot, Dr. Kurth told Neurology Today. “In relative terms, even though migraine with aura is a strong contributor, of course not everyone with migraine with aura will experience a cardiovascular disease event.”